Intrinsically cell-penetrant, autophagy-inducing peptides
Tufts University investigator, Joshua Kritzer, has developed a family of modified peptides that induce the biological process of autophagy. These peptides are potential therapeutics for diseases in which deregulation or dysfunction of autophagy plays a role.
There is a growing need to address autophagy in neurodegenerative disorders, muscular disease, inflammatory bowel disease and other autoimmune disorders. While tissue-specific autophagy gene delivery in liver, muscle, brain or lungs has showing promise in proof-of principle studies, such approaches are not yet readily transferable to human patients.
Dr. Kritzer has developed cyclic peptides that are cell penetrating, and induce cellular autophagy in vitro and in vivo. These peptides have the potential to be used as therapeutics in a wide variety of disorders including less common indications such as lysosomal storage disorders and cystic fibrosis.
Source and Characterization
The peptides are derived from the primary sequence of the autophagy regulator Beclin 1. These include a Tat- 11mer, which represents the most potent Beclin 1-derived peptide inducer of autophagy to date, and DD5- o, a stapled peptide that is intrinsically cell-penetrant. The stapled peptide DD5-o was discovered using a novel, structure-independent stapling strategy. These peptides induce autophagy at low micromolar concentrations in vitro, induce autophagy in vivo (A), and have biological activity in a cellular model of Huntington’s disease (B) (Detailed data: Peraro et al., 2017, PMID: 28414223).
Path to Commercialization
• Industry partners looking to license and develop peptide therapeutics for indications where cellular autophagy is needed
• Funding entities looking to assemble a team for a start-up focused on developing autophagy peptides on its own or in collaboration with other partners
Improved authophagy activity
Published PCT Application WO 2017-161274 (09/21/2017)